The purpose of this proposal is to renew the ICIDR grant funded at the Harvard School of Public Health collaborative investigations with scientists in Brazil. The proposal contains projects on three parasitic diseases importance in South America, schistosomiasis, leishmaniasis and malaria. The goal of the research of all five projects directed at decreasing the morbidity of these diseases through a multidisciplinary approach involving immunology, molecular biology, and vector biology. Work is proposed to define immunological reactivity and haplotype of patients with schistosomiasis for design of more effective vaccine antigens. One project on schistosomiasis extends the HLA typing in our field site in Bahia and determines the antibody and cellular response to native, deglycosylated and recombinant schistosome antigens. The second schistosome project is directed at understanding certain carbohydrates on antigens appear to direct the T cell response shifting it from a Th1 to Th2. To better understand how the disease is transmitted, one project tests the hypothesis that humans may be an important reservoir for visceral and/or cutaneous leishmaniasis (CL) in Northeastern Brazil and an aim of this work is to determine if clinical and subclinical cases can infect the sand fly vector. HLA typing will also be done in an area in Baturite where CL cases are clustered. Two projects are aimed at combating these diseases by improving the efficacy of drug treatment. The project on leishmaniasis proposes a drug trial to compare the effectiveness of allopurinol with glucantime on L. braziliensis in Brazil, extending the promising findings of Martinez and Marr on L. b panamensis in Columbia. The other project on malaria focuses on one of the most critical problems in world health, that of drug resistance, and proposes to characterize the biochemical and molecular basis for drug resistance to malaria in Brazil. We are especially interested in studying quinine resistance which appears to be present there. This is a new project with collaboration of the Fundacao Oswaldo Cruz and USAMRU- B in Rio de Janiero and field site in Mato Grosso.